Abstract
Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathies. In a recent study, we synthesized and established the methylene-cycloalkylacetate (MCAs) pharmacophore as a lead for the development of a neurotropic drug (inducing neurite/axonal outgrowth) using the PC12 neuronal model. In the present study we extended the characterizations of the in vitro neurotropic effect of the derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid (MCA-13) on dorsal root ganglia and spinal cord neuronal cultures and analyzed its safety properties using blood biochemistry and cell counting, acute toxicity evaluation in mice and different in vitro “off-target” pharmacological evaluations. This MCA derivative deserves further preclinical mechanistic pharmacological characterizations including therapeutic efficacy in in vivo animal models of polyneuropathies, toward development of a clinically relevant neurotropic drug.
Original language | English |
---|---|
Pages (from-to) | 2577-2589 |
Number of pages | 13 |
Journal | ACS Chemical Neuroscience |
Volume | 11 |
Issue number | 17 |
DOIs | |
State | Published - 2020 |
Keywords
- DRG
- Enzyme
- GPCR
- Kinome
- Methylene-cycloalkylacetate
- Neurotropic activity
- Off-target
- PC12
- PGE
- Safety
- Spinal cord neuron
- Transporter
All Science Journal Classification (ASJC) codes
- Biochemistry
- Physiology
- Cognitive Neuroscience
- Cell Biology